AIM: To investigate the relationship between visfatin, human serum amyloid A (SAA) and tumor necrosis factor α (TNF-α) and pathogenesis of type 2 diabetic retinopathy (DR). METHODS: Patients with type 2 diabetes mellitus (DM) without DR group comprised 35 individuals. Type 2 DM with nonproliferative DR group included 33 patients and type 2 DM with proliferative DR group was composed of 36 patients. The control group consisted of 40 healthy persons. ELISA was used to detect the contents of visfatin, SAA and TNF-α. RESULTS: The expressions of visfatin, SAA and TNF-α of patients from the 3 patients groups were significantly higher than those from the control group (P<0.01) and a significant difference existed between the patients groups and the control group (P<0.01). There was a positive correlation between these factors and the severity of disease. And the 3 factors were also positively correlated with fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1c) while negatively correlated with insulin concentration. CONCLUSION: Visfatin level of serum from patients with type 2 DR could reflect the fundus vascular endothelial dysfunction and the disease course of arteriosclerosis, which suggests that content of serum visfatin may be closely related with the occurrence and development of ocular fundus arteriosclerosis. And SAA could activate the expression of tissue factor in endothelial cells and monocytes, therefore, the formation of thrombosis and the instability of plaque was accelerated. visfatin and SAA could promote secretion of TNF-α and play the roles of medium in inducing inflammatory reaction. The abnormal expression of the three factors could accelerate the remodeling of internal ophthalmic artery and the growth effect of new intima and promote the disease evolution of type 2 DR.